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CXC Chemokine Receptor-4 Antagonist Blocks Both Growth of Primary Tumor and Metastasis of Head and Neck Cancer in Xenograft Mouse Models

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Author(s)
Younghyoun YoonZhongxing LiangXin ZhangMison ChoeAizhi ZhuHeidi T. ChoDong M. ShinMark M. GoodmanZhuo (Georgia) Chenand Hyunsuk Shim
Keimyung Author(s)
Choe, Mi Sun
Department
Dept. of Pathology (병리학)
Journal Title
Cancer Research
Issued Date
2007
Volume
67
Issue
15
Abstract
Squamous cell carcinoma of the head and neck (SCCHN) metastasizes to the lymph nodes and lungs. We have generated previously an orthotopic mouse model for head and neck metastasis and did in vivo selection of SCCHN cells through four rounds of serial metastases. A subpopulation of 686LN cells with high metastatic potential (686LN-Ms) was isolated. When the highly metastatic cells were compared with their low metastatic parental cells (686LN-Ps), we found that CXC chemokine receptor-4 (CXCR4) mRNA levels were significantly higher in the 686LN-Ms cells than the 686LN-Ps cells. Interestingly, the metastatic subclones had lost epithelial morphology and acquired mesenchymal features, which were maintained during cell expansion in vitro. This was featured by decreased E-cadherin and involucrin and increased vimentin and integrin β1. These results imply that CXCR4 and epithelial-mesenchymal transition markers can be potential biomarkers to identify the subpopulation of cells with high metastatic potential. Using the orthotopic SCCHN animal model, we showed that anti-CXCR4 treatment suppressed primary tumor growth by inhibiting tumor angiogenesis and prevented lung metastasis. Because the reduction of metastasis seen in the treated group could have resulted from 2-fold reduction in primary tumor size compared with that in the control group, we examined the effects of the CXCR4 antagonist in an experimental metastatic animal model in which 686LN-Ms cells were i.v. injected. 686LN-Ms cells failed to metastasize in the CXCR4 antagonist-treated group, whereas they metastasized to the lungs in the control group. Our data indicate that CXCR4 is an important target to inhibit tumor progression in SCCHN. [Cancer Res 2007;67(15):7518–23]
squamous cell carcinoma
CXCR4
tumor angiogenesis
metastasis
epithelial mesenchymal transition
Keimyung Author(s)(Kor)
최미선
Publisher
School of Medicine
Citation
Younghyoun Yoon et al. (2007). CXC Chemokine Receptor-4 Antagonist Blocks Both Growth of Primary Tumor and Metastasis of Head and Neck Cancer in Xenograft Mouse Models. Cancer Research, 67(15), 7518–7524. doi: 10.1158/0008-5472.CAN-06-2263
Type
Article
ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-06-2263
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35329
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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